A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

Jordan Marrocco; Gordon H. Petty; Mariel B. Ríos; Jason D. Gray; Joshua F. Kogan; Elizabeth M. Waters; Eric F. Schmidt; Francis S. Lee; Bruce S. McEwen

doi:10.1038/s41467-017-01014-4

journal article Open Access Oct 09, 2017

A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

Gordon H. Petty Mariel B. Ríos Jason D. Gray Joshua F. Kogan Elizabeth M. Waters Eric F. Schmidt Francis S. Lee Bruce S. McEwen

Nature Communications Vol. 8 No. 1 · Springer Science and Business Media LLC

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Abstract

AbstractMales and females use distinct brain circuits to cope with similar challenges. Using RNA sequencing of ribosome-bound mRNA from hippocampal CA3 neurons, we found remarkable sex differences and discovered that female mice displayed greater gene expression activation after acute stress than males. Stress-sensitive BDNF Val66Met mice of both sexes show a pre-stressed translational phenotype in which the same genes that are activated without applied stress are also induced in wild-type mice by an acute stressor. Behaviourally, only heterozygous BDNF Val66Met females exhibit spatial memory impairment, regardless of acute stress. Interestingly, this effect is not observed in ovariectomized heterozygous BDNF Val66Met females, suggesting that circulating ovarian hormones induce cognitive impairment in Met carriers. Cognitive deficits are not observed in males of either genotype. Thus, in a brain region not normally associated with sex differences, this work sheds light on ways that genes, environment and sex interact to affect the transcriptome’s response to a stressor.

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Published: Oct 09, 2017
Vol/Issue: 8(1)
License: View

Authors

Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Department of Geriatrics and Palliative Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; and Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York

Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Department of Geriatrics and Palliative Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; and Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York

Cite This Article

Jordan Marrocco, Gordon H. Petty, Mariel B. Ríos, et al. (2017). A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice. Nature Communications, 8(1). https://doi.org/10.1038/s41467-017-01014-4

A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

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